Composition for use in treating dystrophic epidermolysis bullosa

Abstract

The present disclosure relates to a composition for use in the treatment of dystrophic epidermolysis bullosa, comprising a cell obtained from a patient with dystrophic epidermolysis bullosa, wherein the cell is a mesenchymal stem cell and genetically modified to produce type VII collagen. The present disclosure also relates to a composition for use in the treatment of dystrophic epidermolysis bullosa, comprising a cell that produces type VII collagen, wherein the composition is to be administered into a blister.

1 - 16 . (canceled) 
     
     
         17 . A method of treating dystrophic epidermolysis bullosa, comprising the steps of:
 (a) obtaining mesenchymal stem cells from a patient with dystrophic epidermolysis bullosa;   (b) genetically modifying the cells to produce type VII collagen; and   (c) administering the cells of (b) to the patient.   
     
     
         18 . The method of  claim 17 , wherein genetically modifying the cells of (b) includes delivering a COL7A1 gene to the cells. 
     
     
         19 . The method of  claim 18 , wherein the COL7A1 gene comprises a nucleic acid sequence having 90% or more sequence identity with the nucleic acid sequence of SEQ ID NO: 1, or a nucleic acid sequence that encodes an amino acid sequence having 90% or more sequence identity with the amino acid sequence of SEQ ID NO: 2. 
     
     
         20 . The method of  claim 17 , wherein the mesenchymal stem cells are bone marrow-derived mesenchymal stem cells. 
     
     
         21 . The method of  claim 17 , wherein administering the cells to the patient comprises administering a population of cells to the patient, wherein the mesenchymal stem cells are the most abundant cells in the population. 
     
     
         22 . The method of  claim 17 , wherein the cells are administered to the patient by intrablister injection. 
     
     
         23 . The method of  claim 22 , wherein the intrablister injection is an injection of the cells into a space formed between the basal membrane and the dermis of the patient's skin, at a place where the basal membrane is detached from the dermis. 
     
     
         24 . A method of treating dystrophic epidermolysis bullosa, comprising:
 administering a therapeutically-effective amount of cells which produce type VII collagen to a patient in need thereof, the administering being intrablister administration.   
     
     
         25 . The method of  claim 24 , wherein the cells have been genetically modified to produce type VII collagen. 
     
     
         26 . The method of  claim 25 , wherein the cells have been genetically modified by delivering a COL7A1 gene to the cells. 
     
     
         27 . The method of  claim 26 , wherein the COL7A1 gene comprises a nucleic acid sequence having 90% or more sequence identity with the nucleic acid sequence of SEQ ID NO: 1, or a nucleic acid sequence that encodes an amino acid sequence having 90% or more sequence identity with the amino acid sequence of SEQ ID NO: 2. 
     
     
         28 . The method of  claim 24 , wherein the cells have been obtained from the patient with dystrophic epidermolysis bullosa. 
     
     
         29 . The method of  claim 24 , wherein the cells have been obtained from bone marrow. 
     
     
         30 . The method of  claim 24 , wherein the cells are mesenchymal stem cells. 
     
     
         31 . The method of  claim 30 , wherein the mesenchymal stem cells are bone marrow-derived mesenchymal stem cells. 
     
     
         32 . The method of  claim 30 , wherein administering the cells to the patient comprises administering a population of cells to the patient, wherein the mesenchymal stem cells are the most abundant cells in the population. 
     
     
         33 . The method of  claim 24 , wherein the intrablister administration is injection of the cells into a space formed between the basal membrane and the dermis of the patient's skin, at a place where the basal membrane is detached from the dermis. 
     
     
         34 . A gRNA comprising a sequence selected from the group consisting of SEQ ID NOs: 3 to 5, or a sequence complementary thereto. 
     
     
         35 . A method of preparing cells for administration to a patient in need of treatment of dystrophic epidermolysis bullosa, comprising:
 genetically modifying mesenchymal stem cells to produce type VII collagen, the cells having been obtained from the patient in need of treatment of dystrophic epidermolysis bullosa,   wherein the genetically modified cells are capable of being administered to the patient.   
     
     
         36 . A method of treating dystrophic epidermolysis bullosa, comprising:
 administering a therapeutically-effective amount of cells which produce type VII collagen to a patient in need thereof, the cells being mesenchymal stem cells having been previously obtained from the patient and genetically modified to produce type VII collagen.